United States Department of

Health & Human Services Office of the Assistant Secretary for Preparedness and Response

Robert C. Huebner, Ph.D. Acting Director – Influenza Division

BARDA/ASPR January 15, 2013

BARDA International and Domestic Capacity Building Activities

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 2

Why do we need to prepare for pandemics?

A(H1N1) A(H2N2) A(H3N2) 1918: “Spanish Flu” 1957: “Asian Flu” 1968: “Hong Kong Flu”

20-100 m deaths ~500,000 in US

1-4 m deaths 60-80,000 in US

1-4 m deaths ~30,000 in US

Credit: US National Museum of Health and Medicine

1976 Swine Flu – The “No-Show Pandemic” “2009 H1N1 Pandemic”

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 3

Requirements are Set • The requirements addressed by the BARDA Influenza Portfolio are

derived from a number of documents that guide the US Government efforts to prepare for pandemics

• National Strategy for Pandemic Influenza (Nov 2005) • HHS Pandemic Influenza Plan (Nov 2005) • Nation Strategy for Pandemic Influenza Implementation Plan (May 2006) • Public Health Emergency Medical Countermeasures Review (Aug 2010) • PCAST report on Reengineering the Influenza Vaccine Production

Enterprise (Aug 2010)

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 4

• Vaccines – Goal #1: Establish and maintain a dynamic pre-pandemic influenza vaccine stockpile

available for 20 M persons (2 doses/person) or more depending on vaccine mfg. capacity, results of dose-sparing adjuvant studies and prime-boost immunization studies: H5N1 vaccine stockpiles - Achieved

– Goal #2: Provide pandemic vaccine to all U.S. citizens within 6 (or less) months of a pandemic declaration: pandemic vaccine (600 M doses)

• Antivirals – Goal #1: Provide influenza antiviral drug stockpiles for pandemic treatment of 25% of U.S.

population (75 M treatment courses) and federal share of antivirals for outbreak prophylactic usage as a community mitigation measure as shared responsibility - Achieved

– Goal #2: Provide influenza antiviral drug stockpiles for strategic limited containment at onset of pandemic (6 M treatment courses) - Achieved

• Diagnostics – Goal #1: Develop new high-throughput laboratory, point-of-care (POC), and home detection

influenza diagnostics for pandemic influenza virus detection • Other Countermeasures

– Goal #1:Develop and acquire other MCMs including syringes/needles, masks/respirators, ventilators & other supplies

National Strategy for Pandemic Influenza (Nov 2005) and HHS Pandemic Influenza Plan (Nov 2005) www.pandemicflu.gov

U.S. Pan Flu MCM Strategic Goals

United States Department of

Health & Human Services Office of the Assistant Secretary for Preparedness and Response

Building on existing egg-based technology –MORE Modernize the influenza manufacturing process – BETTER Use new technology approaches to manufacture influenza

vaccine - FASTER

Vaccine Strategy – leverage seasonal vaccine business

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 6

• The most attainable goal for near term pandemic preparedness ─ Egg Supply Contract (2004)

• Established a year round supply of fertilized eggs for influenza vaccine manufacturing

• Created inventories of other essential supplies (vials, preservative, etc.)

─ Vaccine Stockpile Contracts (2004) • Contracts to produce vaccine for pre-pandemic stockpile and

in the event of a pandemic (2009) • Manufacturing base gains experience producing pandemic

virus vaccine at commercial scale ─ Facility Retrofit Contracts (2007)

• Expanded domestic facilities for inactivated and live-attenuated influenza vaccine production

Egg-based Technology Investments

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 7

• Provide more robust, flexible, and scalable process for manufacturing influenza vaccines

• Awarded 6 contracts in 2005-06 for advanced development of US licensed cell-based seasonal & pandemic influenza vaccines ($1.2B) with commitment for

domestic surge capacity of 150M doses within 6 mos. of pandemic onset

• Novartis, Baxter, sanofi pasteur, GSK, Solvay, MedImmune ─ Novartis vaccine was licensed for 18+ in November 2012 ─ One completed pivotal Phase 3 clinical studies & expected

to submit a BLA in 2013 ─ One manufacturer in early stage development ─ Three programs are no longer active

Cell-based Influenza Vaccines

ASPR: Resilient People. Healthy Communities. A Nation Prepared.

Public Private Partnership Changed U.S. Vaccine Industry

First cell-based influenza vaccine mfg. facility in the U.S. (Novartis): Dedicated as Pandemic Ready in December 2011

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 9

• Adjuvants, immunostimulating molecules, provide dose-sparing effects, cross-strain protection (in animal models) and reactivity in serological assays, and enhanced immune responses to vaccines

• ASPR/BARDA awarded 3 contracts in 2007 ($133 M) for advanced development of US-licensed pandemic influenza vaccines with adjuvants ─ Novartis, GSK, Intercell (formerly IOMAI) ─ One manufacturer (GSK) has completed Phase 3 clinical studies &

submitted a BLA in February 2012 ─ One manufacturer has completed Phase 2 clinical studies ─ One contract is no longer active

< filled vaccine & adjuvant – Production skid >

Antigen Sparing Technology

ASPR: Resilient People. Healthy Communities. A Nation Prepared.

Recombinant & Molecular Vaccine Technologies

• Recombinant & molecular technologies may provide vaccine sooner with less dependence on influenza virus strain properties

• BARDA awarded contracts in 2009 & 2011 for advanced development of US-licensed recombinant- based seasonal & pandemic influenza vaccines with commitment for domestic manufacturing surge capacity of 50 M doses in 6 months of pandemic onset & initial lot release in 12 weeks

• Protein Sciences, Novavax, & VaxInnate ─ One manufacturer completed Phase 3 clinical trials & BLA

submitted ─ Two manufacturers in Phase 2 clinical studies

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 11

• Build or Retrofit Manufacturing Facilities ─ Newly constructed or retrofitted existing facilities in the U.S. will utilize state-of-the art

flexible manufacturing approaches for platform vaccine and biopharmaceutical product technologies

• Provide ADM Core Services for CBRN/Influenza MCMs ─ Upstream & downstream process development, optimization, scale up, and validation ─ Manufacturing process validation ─ Product formulation chemistry ─ Lot release & clinical testing assay development, optimization, and validation ─ Quality systems (Control & Assurance – GMP & GLP compliance) ─ Regulatory affairs (IND, EUA, BLA, NDA submissions & strategy) ─ Clinical investigational lot manufacturing (pilot scale) ─ Commercial scale manufacturing ─ Program management

• Workforce Development Training Program

• Provide Emergency Flexible Vaccine Manufacturing for Pan Flu & Other

Threats – Pandemic influenza vaccine manufacturing capacity should be at least 50 million doses

Centers for Innovation in Advanced Development and Manufacturing

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 12

High return on Investment: $59M USG --> $538M leveraged locally • 14 grantees in 13 countries • 200 scientists trained in advanced biomanufacturing skills

─ Improvements realized in process development and quality systems • 8 manufacturers have initiated human clinical trials

─ In 2012, India, Bangladesh, Vietnam, Thailand, Russia • 6 countries have licensed influenza vaccine

─ In 2012, 1st cGMP licensed vaccine at Butantan (Brazil), WHO Prequalification (India) • 2 countries have adjuvant production capability

─ In 2012, completed production transfer, prepared for tox and future clinical trials

ASPR/BARDA International Vaccine Manufacturing Capacity Building Program

ASPR: Resilient People. Healthy Communities. A Nation Prepared.

Thank You for Your Attention Robert Huebner, Ph.D. Acting Director of Influenza Division Biomedical Advanced Research and Development Authority (BARDA) US Department of Health and Human Services 330 Independence Avenue, SW Room G644 Washington, DC 20201

Robert.Huebner@hhs.gov